DESCRIPTION: Recurrent HSV-1 ocular infections are the leading infectious cause of blindness in industrialized nations. Stress and trauma can reactivate latent HSV-1. The episodes of recurrent ocular infection lead to corneal scarring, loss of visual acuity and possible blindness. We will use a murine model of hyperthermia-induced HSV-1 reactivation to assess the important of transcription factor binding (AP-2 and SP-1) in the first 1536 nucleotides of LAT gene, which has been identified as essential for reactivation. The viral construct 17delta348 (348 bp deleted from the LAT gene) has a low reactivation frequency when compared to the parent strain 17 syn+. The 348 bp region has the high reactivation frequency of the parent strain. An SP-1 site at the 3' end of the 348 bp region is deleted in 17delta348 but not in the smaller deletion mutants. I hypothesize that this site and possibly others function in the reactivation cascade. The specific aims I propose are 1) to determine the reactivation phenotypes of the parent strain 17 syn+ and eight viral constructs in the murine hypothermia in acutely infected, latent and reactivated mice; and 3) to generate a site-directed mutation in the SP-1 site at the 3' end of the 348 bp deletion, determine its reactivation phenotype and the transcription factor profile. These data will lead to the isolation of key genomic sequences that are required for hyperthermic stress-induced reactivation.